HER2 Support Group Forums - PET/CT Shows Tumor Response to Trastuzumab

Journal of Nuclear Medicine Vol. 50 No. 11 1848-1856
© 2009 by Society of Nuclear Medicine
doi: 10.2967/jnumed.109.067231
<TABLE cellSpacing=0 cellPadding=0><TBODY><TR><TD><HR noShade SIZE=1>Basic Science Investigation

</TD></TR></TBODY></TABLE>
18F-FDG Small-Animal PET/CT Differentiates Trastuzumab-Responsive from Unresponsive Human Breast Cancer Xenografts in Athymic Mice

Kristin McLarty1, Aisha Fasih1, Deborah A. Scollard1, Susan J. Done2,3, Douglass C. Vines4,5, David E. Green4, Danny L. Costantini1 and Raymond M. Reilly1,6,7

1 Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada; 2 Department of Medical Biophysics and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; 3 Ontario Cancer Institute and Department of Pathology, University Health Network, Toronto, Ontario, Canada; 4 Radiation Medicine Program, STTARR Innovation Centre, Princess Margaret Hospital, Toronto, Ontario, Canada; 5 Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; 6 Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada; and 7 Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada
Correspondence: For correspondence or reprints contact: Raymond M. Reilly, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College St., Toronto, ON, Canada M5S 3M2. E-mail: raymond.reilly@utoronto.ca<SCRIPT type=text/javascript></SCRIPT>
Breast cancers (BCs) with high human epidermal growth factor receptor type 2 (HER2) expression are most likely to respond to trastuzumab; however, the mechanisms of action of trastuzumab are complex and there are no established biomarkers to accurately monitor treatment outcome in individual patients. Therefore, our aim was to determine, in human BC xenografts in athymic mice treated with trastuzumab, whether there were any changes in 18F-FDG uptake that were associated with response to the drug and that could have utility in monitoring response in patients. Methods: Baseline tumor uptake of 18F-FDG was measured in mice with MDA-MB-361 HER2-overexpressing xenografts and MDA-MB-231 xenografts with low HER2 expression by small-animal PET imaging on day 0. Mice were treated with phosphate-buffered saline (PBS) or trastuzumab (4 mg/kg), and small-animal PET was repeated 2 d after treatment. Maintenance doses of trastuzumab (2 mg/kg) or PBS were administered on days 7 and 14, and mice were imaged again on days 9 and 16. Tumor uptake was measured as percentage injected dose per gram (%ID/g) by volume-of-interest analysis on days 0 (baseline), 2, 9, and 16, followed by biodistribution studies on day 16. Tumor growth was measured, and a tumor growth index was calculated. Results: The treatment of mice with trastuzumab, compared with control mice treated with PBS, resulted in a significant decrease in tumor uptake of 18F-FDG in HER2-overexpressing MDA-MB-361 xenografts after 16 d of treatment (2.6 ± 0.8 %ID/g vs. 4.6 ± 1.8 %ID/g, respectively; P < 0.03) but not after 2 or 9 d of treatment (P = 0.28–0.32). In contrast, there was no significant change in the tumor uptake of MDA-MB-231 xenografts with low HER2 expression during the entire course of therapy (4.4 ± 1.7 %ID/g vs. 3.6 ± 1.1 %ID/g, respectively; P = 0.31). Trastuzumab treatment, compared with PBS treatment of controls, resulted in significant growth inhibition of MDA-MB-361 xenografts as early as 10 d from the initiation of treatment (tumor growth index, 0.7 ± 0.2 vs. 1.7 ± 0.3, respectively; P < 0.0005), whereas no tumor growth inhibition was observed for MDA-MB-231 xenografts (5.3 ± 2.7 and 5.2 ± 3.0; P = 0.95). Conclusion: Changes in the tumor uptake of 18F-FDG after therapy accurately identified responding and nonresponding human BC xenografts in athymic mice treated with trastuzumab; however, diminished glucose utilization did not precede changes in tumor volume. 

Key Words: HER2 • trastuzumab • 18F-FDG • PET • tumor response
COPYRIGHT © 2009 by the Society of Nuclear Medicine, Inc.